Concordance between platelet counts by impedance and optical technique during microcytic anemia: towards a threshold value of the mean corpuscular volume.

INTRODUCTION: Platelet count is crucial for clinical decision. In cases of microcytosis, platelet count based on impedance technique (PLT-I) may overestimate platelet count. AIM: To compare PLT-I with platelet count using the optical technique (PLT-O) and establish a Mean Corpuscular Volume (MCV) threshold for considering PLT-O. METHODS: A prospective analytical study conducted over two months involved blood samples collected in standard K2 EDTA tubes for complete blood count analysis, revealing microcytosis (MCV<80 fL). PLT-O analysis in channel-Ret mode was performed using the Sysmex-XN1000 (Sysmex Corporation, Kobe, Japan). Percentage of fragmented red cells (FRC%) and percentage of microcytic red cells (Micro-R%) were recorded. Blood smears stained with May-Grünwald-Giemsa were examined for potential interfering particles. RESULTS: A strong correlation was observed between the two techniques for all platelet values as well as for PLT <150 x 109/L (correlation coefficient r = 0.971, 95% CI: [0.956-0.982]; P<10-3 and r = 0.90, 95% CI: [0.79-0.95]; P< 10-3). The Bland-Altman plot revealed a bias of 16.53 x 109/L between the two methods, with agreement limits between -55.8 and 88.8 x 109/L. A threshold MCV value indicating the use of the optical method, with a cut-off at 72.9fL, demonstrated promising performance consistent with literature findings. However, less favorable performance was observed with Micro-R%. CONCLUSION: Impedance could be employed in routine practice. However, for MCV<72.9 fL or in the presence of schizocytes, the hemogram validation procedure may incorporate the use of PLT-O.

Association between low MCV in early pregnancy and perinatal mental health in the Japan Environment and Children's Study and the possible effect of iron deficiency.

BACKGROUND: Postpartum anemia and iron deficiency are associated with postpartum depression. This study investigated the association between a low mean corpuscular volume (MCV) without anemia (which implies early-stage iron deficiency) in early pregnancy and perinatal mental health outcomes. METHODS: The fixed data from the Japan Environment and Children's Study (JECS), a Japanese nationwide birth cohort, were used. Perinatal mental health was assessed using the Kessler 6-item psychological distress scale (K6) in mid-pregnancy and the Edinburgh Postnatal Depression Scale (EPDS) at 1- and 6-months postpartum. RESULTS: Among the 3635 women with MCVs <85 fL in early pregnancy, the proportions of women with K6 scores ≥13 in mid-pregnancy and EPDS scores ≥9 at 1- and 6-months postpartum were 2.7 %, 12.8 %, and 9.9 %, respectively, compared with the 33,242 women with MCVs ≥85 fL at 1.9 %, 11.9 %, and 9.0 %, respectively. Multivariate logistic regression models showed that an MCV <85 in early pregnancy was associated with a K6 score ≥ 13 in mid-pregnancy and an EPDS score ≥ 9 at 1- and 6-months postpartum (adjusted odds ratio (95 % confidence interval): 1.48 (1.16-1.87), 1.14 (1.01-1.28), and 1.09 (0.95-1.24), respectively). LIMITATIONS: Low MCV values do not necessarily represent iron deficiency. Ferritin, currently the best indicator of iron deficiency, was not measured in the JECS. CONCLUSIONS: This study results suggest that a low MCV without anemia in early pregnancy is associated with a slightly increased risk of perinatal mental health deterioration.

Association between biomarkers of inflammation and dyslipidemia in drug resistant tuberculosis in Uganda.

BACKGROUND: Active tuberculosis (TB) significantly increases the risk of cardiovascular disease, but the underlying mechanisms remain unclear. This study aimed to investigate the association between inflammation biomarkers and dyslipidemia in patients with drug-resistant TB (DR-TB). METHODS: This was a secondary analysis of data from a cross-sectional multi-center study in Uganda conducted 2021. Participants underwent anthropometric measurements and laboratory tests included a lipid profile, full haemogram and serology for HIV infection. Dyslipidemia was defined as total cholesterol > 5.0 mmol/l and/or low-density lipoprotein cholesterol > 4.14 mmol/l, and/or triglycerides (TG) ≥ 1.7 mmol/l, and/or high density lipoprotein cholesterol (HDL-c) < 1.03 mmol/l for men and < 1.29 mmol/l for women. Biomarkers of inflammation were leukocyte, neutrophil, lymphocyte, monocyte, and platelet counts, as well as neutrophil/lymphocyte (NLR), platelet/lymphocyte, and lymphocyte/monocyte (LMR) ratios, mean corpuscular volume (MCV), and the systemic immune inflammation index (SII) (neutrophil × platelet/lymphocyte). Modified Poisson Regression analysis was used for determining the association of the biomarkers and dyslipidemia. RESULTS: Of 171 participants, 118 (69.0%) were co-infected with HIV. The prevalence of dyslipidemia was 70.2% (120/171) with low HDL-c (40.4%, 69/171) and hypertriglyceridemia (22.5%, 38/169) being the most common components. Patients with dyslipidemia had significantly higher lymphocyte (P = 0.008), monocyte (P < 0.001), and platelet counts (P = 0.014) in addition to a lower MCV (P < 0.001) than those without dyslipidemia. Further, patients with dyslipidemia had lower leucocyte (P < 0.001) and neutrophil (P = 0.001) counts, NLR (P = 0.008), LMR (P = 0.006), and SII (P = 0.049). The MCV was inversely associated with low HDL-C (adjusted prevalence ratio (aPR) = 0.97, 95% CI 0.94-0.99, P = 0.023) but was positively associated with hypertriglyceridemia (aPR = 1.04, 95% CI 1.00-1.08, P = 0.052). CONCLUSIONS: Individuals with dyslipidemia exhibited elevated lymphocyte, monocyte, and platelet counts compared to those without. However, only MCV demonstrated an independent association with specific components of dyslipidemia. There is need for further scientific inquiry into the potential impact of dyslipidemia on red cell morphology and a pro-thrombotic state among patients with TB.

External validation of a red cell-based blood prognostic score in patients with metastatic renal cell carcinoma treated with first-line immunotherapy combinations.

Immunotherapy combinations with tyrosine-kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) had significantly improved outcomes of patients with mRCC. Predictive and prognostic factors are crucial to improve patients' counseling and management. The present study aimed to externally validate the prognostic value of a previously developed red cell-based score, including hemoglobin (Hb), mean corpuscular volume (MCV) and red cell distribution width (RDW), in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI). We performed a sub-analysis of a multicentre retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations. Uni- and multivariable Cox regression models were used to assess the correlation between the red cell-based score and progression-free survival (PFS), and overall survival (OS). Logistic regression were used to estimate the correlation between the score and the objective response rate (ORR). The prognostic impact of the red cell-based score on PFS and OS was confirmed in the whole population regardless of the immunotherapy combination used [median PFS (mPFS): 17.4 vs 8.2 months, HR 0.66, 95% CI 0.47-0.94; median OS (mOS): 42.0 vs 17.3 months, HR 0.60, 95% CI 0.39-0.92; p < 0.001 for both]. We validated the prognostic significance of the red cell-based score in patients with mRCC treated with first-line immunotherapy combinations. The score is easy to use in daily clinical practice and it might improve patient counselling.

Association between asymptomatic Plasmodium falciparum malaria infection, anaemia and mean corpuscular volume of school children in the Volta Region of Ghana.

Background: Although, several studies have reported abnormal Mean Corpuscular Volume (MCV) values and anaemia associated with malaria infections with a focus on Plasmodium falciparum among patients with complicated and uncomplicated malaria, none has looked at the association with asymptomatic malaria. This study aimed to assess this association. Methods: We conducted a cross-sectional study using 3 mL of blood samples from 549 children aged 5-17 years attending 5 schools selected in the Volta Region. Semi-structured questionnaires were administered to the children to obtain demographic data. Blood samples were collected to estimate the children's full blood count (FBC) and malaria status. Data obtained were analysed using STATA 15 software. P-values of less than 0.05 were considered statistically significant. Results: Most of the children in this study (49.9%) had normal MCV (81.3-91.3 fL) with an overall malaria prevalence of 55.6 % (95% CI: 51.3-59.8) and anaemia prevalence of 48.6% (95% CI 44.4-52.9). Most anaemic children had normal MCV (81.3-91.3 fL) (49.8, 95% CI 43.7-56.0). The predicted probability of malaria was highly likely among children with normal MCV (81.3-91.3 fL) but with high variability and uncertainty among those with low MCV (<81.3 fL) and high MCV (>91.3 fL). Conclusion: This study shows a reduced predicted probability of malaria among children with low and high MCV, playing a protective function against malaria. Further studies are required to elucidate the interaction.

The drug-survival of low-dose thioguanine in patients with inflammatory bowel disease: a retrospective observational study.

Background: Thiopurines are commonly used to treat inflammatory bowel disease but withdrawal due to side effects are common. Thioguanine has been suggested to be better tolerated than conventional thiopurines. Objectives: We studied drug-survival of low dose of thioguanine in real-life clinical practice in comparison to conventional thiopurines. Design: Retrospective observational study. Methods: All patients born 1956 and later, and who at least once started thiopurine treatment between 2006 and 2022 were included. A medical chart review was performed that noted drug-survival for every thiopurine treatment attempt. The Mantel-Cox rank test was used to test differences in drug-survival for different thiopurines. Blood chemistry analysis and faecal calprotectin levels were registered for the first 5 years of treatment. Results: In the study population, there was 379 initiated thiopurine treatments (210 for Crohn's disease and 169 for ulcerative colitis) in 307 patients with inflammatory bowel disease (IBD). Low-dose thioguanine (median dose 11 mg; 25-75th percentile 7-19 mg) had been initiated in 31 patients. Overall, when including all thiopurine attempts, thioguanine had the longest drug-survival [Mantel-Cox rank test: thioguanine versus azathioprine p = 0.014; thioguanine versus 6-mercaptopurine (6-MP) p < 0.001]. For second-line thiopurine treatment thioguanine had longer drug-survival than 6-MP (Mantel-Cox rank test: p = 0.006). At 60 months, 86% of the patients who started low-dose thioguanine were still on treatment compared to 42% of the patients who started 6-MP (p = 0.022). The median 6-thioguanine nucleotide levels in patients treated with thioguanine was 364 pmol/8 × 108. Patients on thioguanine treatment showed significantly lower values of median mean corpuscular volume at follow-up than patients treated with azathioprine and 6-MP. Patients treated with 6-MP showed significantly lower levels of FC in the third year of treatment compared to patient treated with azathioprine (59 versus 109 µg/g; p = 0.023), but there was no significant difference in FC levels for thioguanine compared to azathioprine (50 versus 109 µg/g; p = 0.33). Conclusion: Treatment with a low dose of thioguanine is well-tolerated in patients with IBD and had a significantly higher drug-survival than conventional thiopurines.

Low-dose of the immunomodulator drug thioguanine are well tolerated by patients with inflammatory bowel disease Thiopurines are commonly used to treat inflammatory bowel disease but it is common that patients end treatment due to side-effects. The thiopurine thioguanine has been suggested to be better tolerated than other thiopurines. We aimed to study if a low-dose of thioguanine had been tolerated better and used longer than other thiopurines in patients with inflammatory bowel disease at our clinic. In the study population there was 379 initiated thiopurine treatments in 307 patients with inflammatory bowel disease. Among those patients a low-dose thioguanine had been initiated in 31 patients. Overall, when including all thiopurine attempts, thioguanine had longest drug-survival of all thiopurines. For second line thiopurine treatment thioguanine had longer drug-survival than the thiopurine 6-mercaptopurine that are usually used as second line thiopurine treatment. At 60 months, 86% of the patients who started low dose thioguanine was still on treatment compared to 42% of the patients who started 6-mercaptopurine.There was a similar response on inflammatory markers the first five years from starting treatment with thioguanines compared to conventional used thiopurines. We conclude that treatment with a low-dose of thioguanine is well tolerated in patients with inflammatory bowel disease and have a significantly higher drug survival than conventional thiopurines.

Ratio of hemoglobin to mean corpuscular volume: A new index for discriminating between iron deficiency anemia and thalassemia trait.

BACKGROUND: Iron deficiency anemia (IDA) and thalassemia trait (TT) are the most common microcytic and hypochromic anemias. Differentiation between mild TT and early IDA is still a clinical challenge. AIM: To develop and validate a new index for discriminating between IDA and TT. METHODS: Blood count data from 126 patients, consisting of 43 TT patients and 83 IDA patients, was retrospectively analyzed to develop a new index formula. This formula was further validated in another 61 patients, consisting of 48 TT patients and 13 IDA patients. RESULTS: The new index is the ratio of hemoglobin to mean corpuscular volume. Its sensitivity, specificity, accuracy, Youden's Index, area under the receiver operating characteristic curve, and Kappa coefficient in discriminating between IDA and TT were 93.5%, 78.4%, 83.3%, 0.72, 0.97, and 0.65, respectively. CONCLUSION: This new index has good diagnostic performance in discriminating between mild TT and early IDA. It requires only two results of complete blood count, which can be a very desirable feature in under-resourced scenarios.

Prognostic value of pre-operative mean corpuscular volume (MCV) in colorectal cancer.

BACKGROUND: Mean corpuscular volume (MCV) has been shown to have some correlation to oncological outcomes in oesophageal cancer, with high pre-operative MCV associated with disease recurrence. A similar association has previously been reported in colorectal cancer. AIMS: This study is aimed at investigating whether high MCV bears similar relation to post-operative outcome and disease recurrence in colorectal cancer (CRC). METHODS: Patients undergoing elective CRC resection with curative intent between January 2008 and December 2019 were identified from our prospective database. Review of patient demographic details, American Society of Anaesthesiologists (ASA) grade, smoking and alcohol intake were performed. In addition, tumour location and staging, operation performed, pre-operative laboratory data and oncological management of each patient were noted. Post-operative morbidity (Clavien-Dindo (CD) score > 2), 30-day mortality, in-hospital mortality and cancer recurrence were examined and multivariable regression analysis was performed to predict these outcomes. RESULTS: A total of 1,293 CRCs were resected, with 1,159 patients (89.7%) experiencing a hospital course without major morbidity (CD < 3). 30-day mortality rate was less than 1% (12/1293). There were 176 patients (13.6%) with recurrence at follow-up. When multivariable regression analysis was performed, high pre-operative MCV did not predict negative post-operative or oncological outcomes. CONCLUSION: MCV does not appear to be an independent prognostic factor for outcomes following elective CRC resection.

Relationship of Mean Platelet Volume (MPV) and Mean Corpuscular Volume (MCV) with the Outcome of Patients with Acute Exacerbation of COPD.

Background: Mean platelet volume (MPV) reflects the platelet production rate and stimulation, while mean corpuscular volume (MCV) represents the average size of red blood cells. Considering the possibility of the relationship between red cell index changes and different severities of chronic obstructive pulmonary disease (COPD) as well as the uncertainty of the available results in this regard, the present study aimed at evaluating the relationship between MPV and MCV in the outcome of patients with acute exacerbation of COPD (AECOPD). Materials and Methods: In this cross-sectional analytical study, 150 patients with AECOPD that referred to the emergency department (ED) were included in the study. The severity of the disease was recorded using the GOLD classification, and the MPV and the MCV were evaluated based on the reference range of kits in the laboratory. Then, the data were analyzed using SPSS software. Results: The mean MPV and MCV were 9.7±8.3 and 85.9±11.5, respectively, and had no significant difference in different severities of COPD(P>0.05). Moreover, although MCV in survivals with a mean of 88.81±6.47 was higher than that of non-survivals with a mean of 85.77±11.73, and MPV in the non-survivals with a mean of 8.53±9.74 was higher than that of survivals with the mean of 8.86±0.92, this difference was not statistically significant (P>0.05). Conclusion: Overall, the results of this study showed that the mean MPV and MCV did not have any significant relationship with AECOPD and patient outcome.

Hematological Indices in Patients With Goiter: A Cross-Sectional Study in a Tertiary Care Hospital in South India.

Introduction A wide range of haematological abnormalities have been observed in patients with goitre. The aim of the study was to evaluate the abnormalities in haematological parameters among patients with goitre in a tertiary care hospital in south India. Methods This was a cross-sectional study carried out in the pathology department of Chengalpattu Medical College from April 1 to June 30, 2019. The lab reports, including the complete blood count (CBC) and serum thyroid profile that included thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) of all the patients with goitre, were retrieved from the laboratory records. Results were tabulated and analysed. Results Out of a total of 200 patients with thyroid dysfunction, 12 (6%) were males and 188 (94%) were females, with the majority (51.5%) of them in the age group of 30-60 years. Serum TSH levels showed a statistically significant association with red cell distribution width (RCDW) (P-value = 0.000), mean corpuscular volume (MCV) (P-value = 0.020), and total white blood cell (WBC) count (P-value = 0.003) among the patients with goiter. There was no significant association between TSH and other parameters like haemoglobin, packed cell volume (PCV), red blood cell (RBC) count, and platelet (PLT) count. Conclusions Red cell distribution width and mean corpuscular volume are useful haematological parameters that will help clinicians in the early diagnosis and proper treatment of haematological abnormalities seen in patients with goitre.

Can Red Blood Cell and Platelet Parameters Be Associated With Inflammation in Children With Tic Disorder?

OBJECTIVE: Tic disorder (TD) is one of the neurodevelopmental disorders and its etiology has not been fully elucidated. Complete blood count (CBC) values have been used as indicators of a systemic inflammatory response. In our study, we aimed to assess hemogram parameters in drug-naive, comorbidity-free children with TD compared with controls. METHODS: This retrospective study included 62 drug-naive children with TD who had undergone CBC within one month prior to the study. A control group of 48 healthy children, matched for age and gender, without any organic or psychiatric disorders, was included. Statistical analysis was performed by using IBM SPSS Statistics for Windows, Version 22.0 (Released 2013; IBM Corp., Armonk, New York, United States).  Results: Hematocrit (p = 0.044), mean corpuscular volume (p = 0.002), platelet count (p = 0.011), and plateletcrit (p = 0.031) values were significantly higher in the TD group, whereas mean corpuscular hemoglobin concentration (p = 0.00) was significantly lower in the TD group. Additionally, a significant negative correlation was observed between the duration of illness and platelet (p = 0.05, r=-0.282), plateletcrit (p = 0.038, r = -0.295), and neutrophil count (p = 0.006, r = -0.391), while a positive correlation was found between the duration of illness and eosinophil count (p = 0.018, r = 0.336). CONCLUSION: The results revealed several significant differences in hemogram parameters between TD patients and the control group. These may suggest the role of inflammation and/or other underlying mechanisms in TD and may inspire new studies. Future studies with larger and more homogeneous samples, including comprehensive inflammatory markers, may contribute to a deeper understanding of the relationship between inflammation and TD.

Improving the diagnosis of myelodysplastic syndrome by red blood cell parameters

Purpose To investigate the value of red blood cell parameters in Myelodysplastic syndrome (MDS) diagnosis and their relations to MDS subtypes and risk groups. Methods The red blood cell parameter [mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW)] levels [203 MDS, 99 aplastic anemia (AA), 145 megaloblastic anemia (MA)] were collected from a single-center retrospective cohort. The cut-off values, area under the receiver operating characteristic curve (ROC) curve (AUC), sensitivity and specificity of the four parameters were calculated from the ROC. Furthermore, Kruskal–Wallis test and Dunn’s Test were performed to determine erythrocyte parameters in different subtypes and prognostic risks MDS. Results There are significant statistic differences in RDW (P < 0.001), MCH (P = 0.036) and MCHC (P < 0.001) (MDS vs AA); RDW (P = 0.009), MCV (P < 0.001), MCH (P < 0.001) and MCHC (P = 0.001) (MDS vs MA); MCV (P = 0.011) and MCH (P = 0.008) (higher-risk MDS vs lower-risk MDS). Between MDS and MA, the area under the receiver operating characteristic curve (ROC) curve (AUC) values of MCV, MCH, MCHC, RDW were 0.846, 0.855, 0.617, and 0.593. Between MDS and AA, the AUC values of MCH, MCHC, RDW were 0.609, 0.671, and 0.662, respectively. Conclusions The red blood cell parameters contribute to the differential diagnosis of MDS, AA and MA and are related to MDS subtypes and risk groups (AU)

Quantifying microcyte and macrocyte percentages in archived red blood cell volume histogram images.

INTRODUCTION: We sought to quantify percentages of microcytes and macrocytes in archived automated hematology analyzer (AHA) red blood cell (RBC) volume histogram images. METHODS: In preliminary studies, we demonstrated that an on-line application of Gauss' area formula (SketchAndCalc™) measured percentage areas of 20 segments under a computer-generated normal distribution curve (-3.0 standard deviations [SD] to +3.0 SD) with accuracy and precision (Pearson's correlation of measured areas with corresponding theoretical areas r [20] = 0.9962 [p < 0.0001]). Thus, we used SketchAndCalc™ to quantify percentages of microcytes (50-80 fL) and macrocytes (110-200 fL) in archived AHA histogram images in women with previously untreated iron-deficiency anemia (IDA) and previously untreated hemochromatosis. RESULTS: Median microcyte percentages in 13 women with IDA and 13 women with hemochromatosis were 63.6% (range 13.5-76.8) and 6.7% (range 3.4-24.8), respectively (p < 0.0001). Mean macrocyte percentages in women with IDA and hemochromatosis were 8.8% ± 6.1 SD and 33.8% ± 11.7 SD, respectively (p < 0.0001). Spearman's correlations of microcyte percentages with macrocyte percentages, mean corpuscular volume, and mean corpuscular hemoglobin in 26 women were rs [26] = -0.9485, rs [26] = -0.9641, and rs [26] = -0.9036, respectively (each p < 0.0001). CONCLUSIONS: This method of quantifying microcyte and macrocyte percentages could enable other studies of RBC volume subpopulations in archived AHA histogram images.

Age and Red Blood Cell Parameters Mainly Explain the Differences Between HbA1c and Glycemic Management Indicator Among Patients With Type 1 Diabetes Using Intermittent Continuous Glucose Monitoring.

BACKGROUND: Glycated hemoglobin (HbA1c) is the gold standard to assess glycemic control in patients with diabetes. Glucose management indicator (GMI), a metric generated by continuous glucose monitoring (CGM), has been proposed as an alternative to HbA1c, but the two values may differ, complicating clinical decision-making. This study aimed to identify the factors that may explain the discrepancy between them. METHODS: Subjects were patients with type 1 diabetes, with one or more HbA1c measurements after starting the use of the Freestyle Libre 2 intermittent CGM, who shared their data with the center on the Libreview platform. The 14-day glucometric reports were retrieved, with the end date coinciding with the date of each HbA1c measurement, and those with sensor use ≥70% were selected. Clinical data prior to the start of CGM use, glucometric data from each report, and other simultaneous laboratory measurements with HbA1c were collected. RESULTS: A total of 646 HbA1c values and their corresponding glucometric reports were obtained from 339 patients. The absolute difference between HbA1c and GMI was <0.3% in only 38.7% of cases. Univariate analysis showed that the HbA1c-GMI value was associated with age, diabetes duration, estimated glomerular filtration rate, mean corpuscular volume (MCV), red cell distribution width (RDW), and time with glucose between 180 and 250 mg/dL. In a multilevel model, only age and RDW, positively, and MCV, negatively, were correlated to HbA1c-GMI. CONCLUSION: The difference between HbA1c and GMI is clinically relevant in a high percentage of cases. Age and easily accessible hematological parameters (MCV and RDW) can help to interpret these differences.

Assessing mean corpuscular volume as a screening tool for gestational vitamin B12 deficiency based on NHANES.

Vitamin B12 can lead to neurological deficits. We assessed whether the mean corpuscular volume (MCV) could be a sufficiently sensitive measurement for abnormal serum methylmalonic Acid (MMA) and total plasma homocysteine (tHCY) (biomarkers of vitamin B12 or folate deficiency) and if so, at what cutoff value. A total of 26,397 participants (12,730 males and 13,667 females) were included in the analysis. Weighted analysis was performed using NHANES data to calculate crude/adjusted associations between MCV-MMA/tHCY, using linear regression. Unadjusted odds ratios (OR) 95% CIs were estimated from logistic regression models. Receiver Operating Curve and the Youden Index were used to identify the MCV level that most accurately distinguished those with abnormal MMA and tHCY (dependent variables) from those without. A positive and significant correlation between MCV-MMA/tHCY was found in the general population between ages 18-85, 0.95 (95% C.I. 0.75-1.17) and 2.61 (95% C.I. 2.15-3.08). In pregnant women, for every unit increase in MCV there was a 19% increase in odds of abnormal MMA, OR 1.19 (95% C.I. 1.08-1.31), p=0.001 and the Area Under the Curve for MCV as a test for abnormal MMA was 78%. An MCV cutoff of 93.1 correctly identified abnormal MMA in pregnant women with 81% sensitivity and 77% specificity. In the general population the MCV test performed poorly in identifying abnormal MMA/tHCY. MCV is an inexpensive measurement that may be useful to screen asymptomatic pregnant women for vitamin B12 abnormalities. This may have a significant impact on reducing adverse neurological outcomes in their children.

Identifying Clinical Predictors of Proliferative Sickle Cell Retinopathy.

PURPOSE: To identify systemic and/or ophthalmologic predictors of proliferative sickle retinopathy. METHODS: Cross-sectional study comparing clinical, laboratory, and structural choriorretinal aspects between sickle cell disease patients with and without proliferative retinopathy. Patients underwent complete systemic and ophthalmologic evaluation. Enhanced depth spectral domain optical coherence tomography with choroidal binarization and optic coherence tomography angiography were performed and choriorretinal vascular components were compared. RESULTS: Forty-five eyes from 45 sickle cell patients were included. Ninety-one percent of patients were diagnosed with sickle cell retinopathy, 29% with proliferative retinopathy. Mean corpuscular volume, lactate dehydrogenase, and percentage of fetal hemoglobin were reduced in the subgroup of patients with proliferative retinopathy when compared with patients without proliferative retinopathy (p ≤ 0.001; p = 0.04; p ≤ 0.001, respectively). The best predictor of proliferative retinopathy was mean corpuscular volume (AUC = 0.842; p = 0.001), followed by the percentage of fetal hemoglobin (AUC = 0.763, p = 0.009) and lactate dehydrogenase (AUC curve = 0.706; p = 0.039). No differences were found between groups in the quantitative analysis of retinal vascularization using OCTA and choroidal vascularization using OCT (p ≥ 0.05). CONCLUSION: Fetal hemoglobin and mean corpuscular volume may be good predictors of proliferative sickle retinopathy. The association between proliferative retinopathy and reduced levels of lactate dehydrogenase and mean corpuscular volume points to hypoxia and not hemolysis as a possible driving force in its pathophysiology.

Prognostic significance of mean corpuscular volume in patients with pancreatic ductal adenocarcinoma and multimodal treatment.

AIM OF THE STUDY: Mean corpuscular volume (MCV) has shown mounting evidence as a prognostic indicator in a number of malignancies. The aim of this study was to examine the prognostic potential of pretherapeutic MCV among patients with pancreatic ductal adenocarcinoma (PDAC) who underwent upfront resection or resection after neoadjuvant treatment (NT). PATIENTS AND METHODS: Consecutive patients with PDAC who underwent pancreatic resection between 1997 and 2019 were included in this study. Neoadjuvantly treated patients' serum MCV was measured before NT and before surgery. In patients undergoing upfront resection serum MCV was measured before surgery. Median MCV values were used as cut-off to distinguish high from low MCV values. RESULTS: Five hundred and forty-nine (438 upfront resected and 111 neoadjuvantly treated) patients were included in this study. Multivariate analysis revealed, that high MCV before and after NT, were independent negative prognostic factors for overall survival (P<0.01, respectively). Furthermore, the median MCV value from before to after NT increased significantly (P<0.001, Wilcoxon signed-rank test) and was (P=0.03, Wilcoxon rank sum test) associated with tumor response to NT. CONCLUSION: High MCV is an independent adverse prognostic factor in patients with resectable neoadjuvantly treated PDAC and may qualify as useful indicator to help physicians to provide personalized prognostication.

Potential modifications of the PLASMIC scoring system for predicting thrombotic thrombocytopenic purpura: Sometimes, less is more.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening occlusive disease of the microcirculation characterized by systemic platelet plugs, organ ischemia, deep thrombocytopenia, and fragmentation of erythrocytes. One of the widely used scoring system to determine the clinical probability of TTP is the PLASMIC scoring system. This study aimed to evaluate the contribution of PLASMIC score modifications to sensitivity and specificity in patients with microangiopathic hemolytic anemia (MAHA) undergoing plasma exchange with a prediagnosis of TTP at our center. MATERIALS AND METHODS: The data of patients who were hospitalized with a previous diagnosis of MAHA and TTP and underwent plasma exchange at Bursa Uludag University, Faculty of Medicine, Department of Hematology between January 2000 and January 2022 were retrospectively analyzed. RESULTS: Overall, 33 patients (including 15 and 18 with and without TTP, respectively) were included in this study. Receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) for the original PLASMIC score was 0.985 (95% confidence interval [95% CI]: 0.955-1.000), and AUC for the PLASMIC score without mean corpuscular volume (MCV) was 0.967 (95% CI: 0.910-1.000), which is close to the original AUC. With the removal of MCV from the scoring system, the sensitivity decreased from 100% to 93%, whereas the specificity increased from 33% to 78%. CONCLUSIONS: Based on the results of this validation study, removing MCV from the PLASMIC score led to the categorization of eight non-TTP cases in the low-risk category, and this could avoid unnecessary plasma exchange. However, in our study increasing the specificity was at the expense of the sensitivity by missing one patient with this new scoring system without MCV. Further multicenter studies with large sample sizes are required owing to the fact that different parameters may be effective in TTP prediction among different populations.

A validation and modification of PLASMIC score by adjusting the criteria of mean corpuscular volume and international normalized ratio.

BACKGROUND: The PLASMIC score was developed for distinguishing thrombotic thrombocytopenic purpura (TTP) from other types of thrombotic microangiopathy. However, two components of the PLASMIC score, mean corpuscular volume (MCV) and international normalized ratio (INR), showed non-significant differences between TTP and non-TTP patients in previous validations. Here, we validate the PLASMIC score and aim to modify it by adjusting the criteria of MCV and INR. MATERIALS AND METHODS: A retrospective validation of suspected TTP patients was performed by reviewing electronic medical records from two medical centers in Taiwan. The performance of different modified types of the PLASMIC score was carried out. RESULTS: Among 50 patients included in the final analysis, 12 were diagnosed with TTP based on deficiency of ADAMTS13 activity and clinical judgement. When stratified by high (score ≥ 6) and low-intermediate risk (score < 6), the positive predictive value (PPV) of the PLASMIC score to predict TTP was 0.45 (95% confidence interval [CI]: 0.29-0.61). The area under curve (AUC) was 0.70 (95% CI: 0.56-0.82). When adjusting the criteria of the PLASMIC score from MCV < 90 fL to MCV ≥ 90 fL, the PPV increased to 0.57 (95% CI: 0.37-0.75). The AUC was 0.75 (95% CI: 0.61-0.87). When adjusting the INR from >1.5 to >1.1, the PPV increased to 0.56 (95% CI: 0.39-0.71). The AUC was 0.81 (95% CI: 0.68-0.90). CONCLUSION: MCV ≥ 90 fL and/or INR > 1.1 might be suitable modifications for PLASMIC score but should be validated in a larger sample size.

Anemia and Poor Iron Indices Are Associated With Susceptibility to Febrile Seizures in Children: A Systematic Review and Meta-analysis.

Introduction: Febrile seizures are the most common type of seizure in children under the age of 5, and a number of risk factors for this condition have been identified. Several studies have examined the connection between iron deficiency anemia and febrile seizures in children, with inconsistent results. As a result, the authors sought to determine the precise link between iron deficiency anemia and its indices (mean corpuscular volume, serum iron, total iron-binding capacity, and ferritin) in conjunction to febrile seizures. Methods: A systematic literature search from several databases (PubMed, Europe PMC, ScienceDirect) was conducted from database inception until November 30, 2022. Studies were eligible if they investigated the relationship of the iron deficiency anemia and the aforementioned indices with the likelihood of febrile seizures. Results: This meta-analysis comprised 20 case-control studies with a total of 3856 participants. Our study revealed that iron deficiency anemia, low mean corpuscular volume, low serum iron, high total iron-binding capacity, and low ferritin were associated with the incremental risk of developing febrile seizures, with the odds ratios ranging from 1.24 to 1.59. Moreover, diagnostic test accuracy meta-analysis indicated that low serum ferritin level had the highest overall area under the curve value amid other iron deficiency anemia indices regarding our outcomes of interest. Conclusion: This study suggest that iron deficiency anemia and poor iron indices are associated with increased risk of febrile seizures in children.